Affinage

TXN

Thioredoxin · UniProt P10599

Length
105 aa
Mass
11.7 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TXN (thioredoxin-1) is a redox-active dithiol protein that functions as a central antioxidant and pro-survival regulator, coupling cellular thiol-reduction capacity to stress-signaling and apoptotic decisions (PMID:7953744, PMID:20202476). Its best-defined mechanism is binding and inhibition of the apoptosis signal-regulating kinase ASK1: under basal conditions TXN holds ASK1 in an inactive inhibitory complex, and conditions that dissociate or deplete TXN release ASK1 to drive JNK/p38-dependent mitochondrial apoptosis (PMID:20202476, PMID:23319048, PMID:24374359). This ASK1/JNK-p38 axis recurs across diverse stress settings, where TXN overexpression suppresses kinase activation and cell death and TXN loss sensitizes cells (PMID:18281606, PMID:38151083). TXN acts as a downstream effector of the Nrf2 antioxidant program, with Nrf2-deficient cells losing TXN and becoming hypersensitive to ASK1/JNK/p38 activation (PMID:20202476), and it is a direct transcriptional target of FOXO1, which coordinately reciprocally regulates TXN and its inhibitor TXNIP (PMID:30962862). TXN itself feeds back on FOXO1 by limiting p300-mediated FOXO1 acetylation and nuclear translocation, identifying FOXO1 as a major oxidative-stress effector controlled by TXN (PMID:27132507). TXN expression is transcriptionally induced by oxidative stress (UVB, H2O2) through a novel cis-acting promoter element bound by a specific nuclear factor (PMID:7797250, PMID:8759006). Beyond the cytoplasm, TXN undergoes ERK1/2-dependent, TXNIP-gated nuclear translocation (PMID:24376827), where it enhances HIF-1α DNA-binding activity by reducing Ref-1/APE1 to promote glycolytic gene expression and drug resistance (PMID:25656992). At the cell surface TXN physically binds MIF and functions as a component of the MIF internalization/receptor machinery required for MIF-mediated TNF-α production (PMID:19601712). A truncated form, Trx80 (N-terminal 80 residues), acts as a redox-independent cytokine on CD14+ monocytes, driving their proliferation, IL-12 secretion, and differentiation through p38/ERK/JNK MAP-kinase signaling (PMID:11342447, PMID:12650942, PMID:15494431). Distinct mitochondrial thioredoxin-2 is essential for viability, acting upstream of cytochrome c release and the intrinsic caspase-9/-3 apoptotic cascade (PMID:11927553).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1994 Medium

    Established that thioredoxin's neuroprotective and GSH-promoting actions require its enzymatic thiol-reductase activity, distinguishing a redox-dependent extracellular function.

    Evidence Conditioned-medium transfer and recombinant ADF/TRX addition with a reducing-inactive mutant, plus neuron survival and intracellular GSH assays

    PMID:7953744

    Open questions at the time
    • Molecular receptor or uptake route for secreted TRX not defined
    • In vivo neuroprotection not tested
  2. 1996 Medium

    Defined how oxidative stress induces TXN at the transcriptional level by mapping a novel cis-acting promoter element distinct from known stress consensus sequences.

    Evidence CAT reporter deletion analysis and EMSA in human cells

    PMID:7797250 PMID:8759006

    Open questions at the time
    • The specific binding transcription factor was not molecularly identified
    • Element's relationship to later-defined Nrf2/FOXO1 regulation unresolved
  3. 2002 High

    Showed the mitochondrial thioredoxin paralog is essential for viability and gates the intrinsic apoptotic pathway, situating thioredoxin upstream of cytochrome c release.

    Evidence Conditional TRX-2 knockout in DT40 cells with ROS, cytochrome c release, caspase assays, and co-IP

    PMID:11927553

    Open questions at the time
    • This concerns the mitochondrial TRX-2 paralog, not cytoplasmic TXN/TRX-1
    • Direct molecular target of TRX-2 in the cascade not identified
  4. 2004 High

    Identified a redox-independent cytokine role for the truncated Trx80 fragment in monocyte activation and differentiation via MAP-kinase signaling.

    Evidence Active-site Cys→Ser mutagenesis, PBMC proliferation/cytokine ELISA, flow cytometry, and MAP-kinase phosphorylation Western blot

    PMID:11342447 PMID:12650942 PMID:15494431

    Open questions at the time
    • The Trx80 cell-surface receptor is unidentified
    • Protease generating Trx80 in vivo unknown
  5. 2009 High

    Demonstrated a direct physical TRX-MIF interaction and that cell-surface TRX serves as part of the MIF internalization/receptor machinery driving inflammatory cytokine output.

    Evidence BIAcore binding, reciprocal co-IP, and anti-TRX antibody blocking of MIF internalization and TNF-α production

    PMID:15081538 PMID:19601712

    Open questions at the time
    • Stoichiometry and structural basis of the TRX-MIF complex not defined
    • How surface TRX is presented and retained is unclear
  6. 2013 Medium

    Consolidated the TRX-ASK1 inhibitory complex as the redox switch for apoptosis, showing complex dissociation and ASK1 Thr845 phosphorylation activate JNK/p38 death signaling.

    Evidence SCO2 and pharmacological/flavonoid perturbations with ASK1 complex-dissociation and phospho-ASK1 assays, kinase assays, and xenografts

    PMID:18281606 PMID:23319048 PMID:24374359

    Open questions at the time
    • Direct redox chemistry of the TRX-ASK1 disulfide handoff not reconstituted here
    • Quantitative threshold of oxidation triggering release undefined
  7. 2015 Medium

    Revealed a nuclear function whereby TRX-1, after ERK1/2- and TXNIP-gated translocation, reduces Ref-1/APE1 to enhance HIF-1α DNA binding and glycolytic gene expression.

    Evidence Immunofluorescence, nuclear/cytoplasmic fractionation, TXNIP overexpression/knockdown, MEK inhibitors, HIF-1α DNA-binding assay, and xenografts

    PMID:24376827 PMID:25656992

    Open questions at the time
    • Nuclear import mechanism / NLS of TRX-1 not defined
    • Direct evidence that Ref-1 reduction is rate-limiting for HIF-1α not isolated
  8. 2016 High

    Positioned TXN within a feedback loop with FOXO1, showing TXN restrains p300-mediated FOXO1 acetylation/nuclear translocation while FOXO1 directly transcribes TXN and TXNIP.

    Evidence Double siRNA epistasis, FOXO1 acetylation/translocation assays, ChIP for FOXO1 at TXN/TXNIP loci, CRISPR knockin/knockout, and PX-12

    PMID:27132507 PMID:30962862

    Open questions at the time
    • Whether TXN acts on FOXO1 via direct disulfide reduction not shown
    • Tissue specificity of the FOXO1-TXN-TXNIP loop incompletely mapped
  9. 2016 Medium

    Extended TRX-1 into multiprotein signaling assemblies coupling redox-dependent ASK1 and TGF-β pathways relevant to metabolic regulation.

    Evidence Co-IP of a TRX-1/MPK38/ASK1/SMAD/ZPR9 complex plus adenoviral rescue in obese mice

    PMID:26421442

    Open questions at the time
    • Direct binary contacts within the complex not resolved
    • Single Co-IP-based complex without structural validation
  10. 2023 Medium

    Generalized TXN as the convergent effector of multiple upstream regulators (ALDH1L2, miRNA, polysaccharide, metabolic inputs) controlling ROS/ASK1-dependent survival and therapy resistance.

    Evidence Co-IP, siRNA/RNAi knockdown, luciferase reporter, PX-12 inhibition, and in vivo cancer/OA/PD models

    PMID:24147004 PMID:29960099 PMID:35597868 PMID:37298317 PMID:38151083

    Open questions at the time
    • These are largely correlative or single-lab pathway placements
    • Direct enzymatic substrates for most contexts not biochemically defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identity of the surface receptors for full-length TRX and Trx80, the structural basis of the TRX-ASK1 redox handoff, and the import machinery for nuclear TRX-1 remain unresolved.
  • No receptor identified for secreted TRX or Trx80
  • No structural model of TRX-ASK1 or TRX-MIF complexes
  • Nuclear translocation machinery uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0016209 antioxidant activity 2 GO:0016491 oxidoreductase activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005576 extracellular region 2 GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ALDH1L2APEX1ASK1FOXO1MIFMPK38TXNIPZPR9
Complex memberships
TRX-1/MPK38/ASK1/SMAD/ZPR9 complexTRX-ASK1 inhibitory complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 ADF/TRX (human thioredoxin) is actively secreted from astrocytoma cells (U251) upon H2O2 exposure; recombinant ADF with intact reducing activity (but not a reducing-inactive mutant) promotes survival of embryonic cortical and striatal neurons in vitro and increases intracellular GSH levels, demonstrating that the neuroprotective function requires thiol-reductase activity. Conditioned medium transfer, recombinant protein addition, mutant ADF lacking reducing activity, intracellular GSH measurement Brain research Medium 7953744
1995 ADF/TRX gene expression is induced by oxidative stress (UVB, H2O2) in human keratinocytes and HTLV-1+ T-cell lines at both mRNA and protein levels. Immunohistochemistry, Western blot, in situ hybridization Immunology letters Medium 7797250
1996 The ADF/TRX gene is transcriptionally upregulated by oxidative stress through a novel cis-acting element located between −976 and −890 in the 5′ promoter, distinct from known stress-response consensus sequences, and bound by a specific nuclear factor identified by gel mobility shift assay. CAT reporter deletion analysis, gel mobility shift assay (EMSA) Nucleic acids research Medium 8759006
2001 Truncated thioredoxin (Trx80, N-terminal 80 residues of TXN) acts as a mitogenic cytokine specifically on CD14+ monocytes (not B or T cells): it increases surface antigens (CD14, CD40, CD54, CD86), promotes monocyte proliferation, and induces IL-12 secretion synergistically with IL-2 to direct a Th1 immune response; full-length Trx does not have this effect. Flow cytometry, proliferation assay, ELISA for cytokines, PBMC culture with purified recombinant proteins Blood Medium 11342447
2002 Mitochondria-specific TRX-2 (thioredoxin-2) is essential for cell viability: conditional TRX-2 knockout in chicken DT40 B-cells causes ROS accumulation, cytochrome c release, and activation of caspase-9 and caspase-3 (but not caspase-8), placing TRX-2 upstream of the intrinsic (mitochondrial) apoptosis pathway. Trx-2 and cytochrome c co-immunoprecipitate in vitro. Conditional gene knockout (tet-off system), ROS measurement, cytochrome c release assay, caspase activity assays, co-immunoprecipitation The EMBO journal High 11927553
2003 Trx80 mitogenic cytokine activity on PBMC (IL-12, IFN-γ induction and proliferation) is independent of its thiol oxidoreductase activity: active-site Cys→Ser double mutant (Trx80SGPS) and structural Cys72Ser mutant both retain full cytokine activity; Trx80 dimerization is non-covalent (no intermolecular disulfide). Site-directed mutagenesis of active-site cysteines, PBMC proliferation assay, ELISA for IL-12 and IFN-γ FEBS letters High 12650942
2004 Trx80 induces differentiation of CD14+ monocytes into a novel cell type (TAMs) distinct from classical iDCs: TAMs show high CD14/CD1a/mannose receptor expression, increased pinocytic capacity, elevated TNF-α/IL-1β/IL-6/IL-10 secretion, and reduced allogeneic T-cell stimulation. This differentiation is mediated through phosphorylation of MAP kinases p38, ERK, and JNK by Trx80. Flow cytometry, cytokine ELISA, pinocytosis assay, allogeneic proliferation assay, Western blot for MAP kinase phosphorylation Blood Medium 15494431
2004 TRX and MIF (macrophage migration inhibitory factor) interact functionally: TRX-overexpressing Jurkat cells are resistant to H2O2-induced apoptosis and show reduced MIF/GIF expression, while CD4+ T cells from MIF-/- mice show elevated intracellular TRX, demonstrating a reciprocal regulatory relationship between TRX and MIF under oxidative stress. Stable transfection, flow cytometry/Western blot, MIF-/- mouse-derived T cells Immunology letters Medium 15081538
2006 TRX-1 overexpression in transgenic mice suppresses IgE/antigen-stimulated histamine release from mast cells and reduces intracellular ROS generation in those cells, without affecting IL-6 or TNF-α cytokine production, indicating that TRX-1 specifically regulates ROS-dependent early signaling events in the FcεRI pathway. TRX-transgenic mouse model, histamine ELISA, intracellular ROS measurement, cytokine ELISA Cell research Medium 16474438
2008 TRX-1 differentially regulates UV radiation effects on MMP-1 and collagen Iα1 in human dermal fibroblasts: Trx inhibits UVA-induced MMP-1 upregulation via NF-κB-dependent mechanism, and inhibits UVB- and IRA-induced collagen Iα1 reduction, but through distinct transcriptional pathways. UV irradiation of primary human fibroblasts, Trx overexpression, NF-κB pathway inhibition, gene expression analysis Experimental gerontology Low 18524517
2008 TRX-ASK1-JNK signaling mediates cell density-dependent cigarette smoke extract (CSE) cytotoxicity in human bronchial epithelial cells: CSE activates ASK1, JNK, and p38 only in subconfluent (not confluent) cells; siRNA knockdown of JNK1/2 or JNK inhibitor attenuates CSE-induced death; TRX overexpression (Tet-on) attenuates CSE-induced cell death and JNK activation, placing TRX upstream of ASK1/JNK in this pathway. siRNA knockdown of JNK1/2, JNK/p38 pharmacological inhibitors, inducible TRX overexpression (Tet-on), Western blot for kinase activation, cell death assay American journal of physiology. Lung cellular and molecular physiology Medium 18281606
2009 TRX-1 physically interacts with MIF (macrophage migration inhibitory factor): BIAcore assay confirms specific TRX-MIF binding; TRX and MIF co-immunoprecipitate from ATL-2 cell lysates and supernatant; cell-surface TRX facilitates MIF internalization (blocked by anti-TRX antibody); anti-TRX antibody inhibits MIF-mediated TNF-α production from macrophages, demonstrating that cell-surface TRX acts as a component of the MIF receptor/internalization machinery. Co-immunoprecipitation, BIAcore binding assay, anti-TRX antibody blocking of MIF internalization and signaling, TNF-α ELISA Antioxidants & redox signaling High 19601712
2010 The Nrf2/Trx axis counteracts ASK1 activation: Nrf2-deficient MEFs have undetectable Trx levels and are hypersensitive to paraquat-induced ASK1/JNK/p38 activation and cell death, while Keap1-deficient MEFs (constitutively high Trx) are more resistant; sulforaphane-induced Nrf2 activation increases Trx and protects SH-SY5Y cells, placing Trx as an effector downstream of Nrf2 that binds and inhibits ASK1. Nrf2-/- and Keap1-/- MEFs (genetic models), siRNA for ASK1, pharmacological JNK/p38 inhibitors, Western blot, cell death assay Free radical biology & medicine High 20202476
2013 SCO2 (a p53 target) promotes apoptosis by inducing dissociation of the TRX-ASK1 inhibitory complex and phosphorylation of ASK1 at Thr845, activating downstream MAP2K4/7 and MAP2K3/6 to trigger JNK/p38-dependent apoptosis in cancer cells. Tumor xenograft model, SCO2 overexpression, ROS measurement, Western blot for ASK1 phosphorylation and TRX-ASK1 complex dissociation, kinase assays Molecular and cellular biology Medium 23319048
2013 TRX-1 nuclear translocation under nitrosative/oxidative stress is dependent on ERK1/2 MAP kinase activation and is controlled by TXNIP expression levels: ERK1/2 activation leads to TXNIP downregulation, which permits TRX-1 nuclear migration; MEK inhibitors (PD98059, UO126) or cytoplasmic ERK anchoring (PEA-15) prevent both TXNIP downregulation and TRX-1 nuclear translocation; TXNIP overexpression blocks nuclear TRX-1, while TXNIP silencing promotes nuclear TRX-1 even without stress. Immunofluorescence localization, MEK inhibitors, TXNIP overexpression and siRNA knockdown, ERK cytoplasmic anchor (PEA-15), TXNIP promoter assay PloS one Medium 24376827
2015 Intranuclear TRX-1 enhances HIF-1α DNA-binding activity by interacting with and reducing Ref-1 (APE1), leading to upregulation of glycolysis-related proteins (PDHK1, HKII, LDHA) and contributing to hypoxia-induced drug resistance in HepG2 cells; GL-V9 reverses resistance by inhibiting TRX-1 nuclear translocation and the TRX-1/Ref-1 axis. Hypoxia drug-resistance cell model, Western blot, nuclear/cytoplasmic fractionation, HIF-1α DNA-binding assay, GL-V9 pharmacological inhibition, in vivo xenograft Free radical biology & medicine Medium 25656992
2016 TXN (TRX-1) overexpression in OxPhos-DLBCL cells curtails p300-mediated FOXO1 acetylation and its nuclear translocation in response to oxidative stress, attenuating FOXO1 transcriptional activity toward apoptosis/cell cycle genes; TXN-depleted OxPhos cells showed greater sensitivity to ROS and doxorubicin, and FOXO1 knockdown in TXN-silenced cells reduced ROS-induced apoptosis, identifying FOXO1 as the major oxidative stress effector regulated by TXN. TXN siRNA knockdown, FOXO1 siRNA knockdown, FOXO1 acetylation assay, nuclear translocation assay, BCL6 ChIP for TXN promoter, cell death assays Oncogene Medium 27132507
2016 TRX-1 forms a multiprotein complex with MPK38, ASK1, SMADs, and ZPR9 that coordinately activates redox-dependent ASK1 and TGF-β signaling; adenoviral delivery of SMAD3 or ZPR9 restores downregulated ASK1 and TGF-β signaling in obese mice, improving glucose and lipid metabolism. Co-immunoprecipitation of multiprotein complex, adenoviral gene delivery in obese mouse models, metabolic phenotyping Antioxidants & redox signaling Medium 26421442
2019 FOXO1 is a direct transcriptional regulator of both TXNIP and TXN (TRX-1): chromatin immunoprecipitation identified TXNIP and TXN as direct FOXO1 transcriptional targets; FOXO1 knockin in HK-2 cells decreased TXNIP and increased TRX levels under high glucose, while FOXO1 KO had opposite effects; the protection was reversed by TRX inhibitor PX-12 or TXNIP siRNA. ChIP for FOXO1 at TXNIP and TXN loci, CRISPR/Cas9-mediated FOXO1 knockin/knockout, siRNA for TXNIP, pharmacological TRX inhibition (PX-12), transgenic mouse model Oxidative medicine and cellular longevity High 30962862
2013 TRX-1 down-regulation by the flavonoid LW-214 in MCF-7 cells releases ASK1, leading to sustained JNK phosphorylation, increased ROS, and activation of the mitochondrial apoptosis pathway (Bax/Bcl-2 ratio, ΔΨm loss, caspase-9 activation, cytochrome c release); TRX-1 overexpression attenuates LW-214-induced JNK activation and apoptosis, confirming TRX-1 as a functional inhibitor of ASK1 upstream of JNK. TRX-1 overexpression, Western blot for ASK1/JNK/apoptosis markers, ROS measurement, JNK inhibitor (SP600125), in vivo xenograft Biochemical pharmacology Medium 24374359
2022 ALDH1L2 interacts with TXN (thioredoxin) and regulates downstream NF-κB signaling; decreased ALDH1L2 expression induces radioresistance in colorectal cancer cells by inhibiting ROS-mediated apoptosis, and TXN inhibitor PX-12 overcomes this radioresistance, demonstrating TXN as the functional mediator of ALDH1L2-regulated NF-κB signaling and radiation response. Co-immunoprecipitation (ALDH1L2–TXN interaction), immunofluorescence, flow cytometry, colony formation assay, PX-12 pharmacological inhibition, xenograft model British journal of cancer Medium 35597868
2023 TXN is targeted by astragalus polysaccharides (APS) as the mechanistic basis for chondrocyte protection: co-immunoprecipitation and immunofluorescence demonstrated that TXN is required for APS-mediated inhibition of the ROS/ASK1/p38 MAPK apoptosis pathway; TXN silencing completely blocked the protective effects of APS on chondrocytes. Co-immunoprecipitation, immunofluorescence localization, TXN siRNA knockdown, ASK1/p38 western blot, in vivo OA model International journal of biological macromolecules Medium 38151083
2013 miR-525-3p-mediated suppression of TXN1 (thioredoxin-1) is required for cell survival following ionizing radiation: luciferase reporter assays confirmed TXN1 as a direct miR-525-3p target; RNAi knockdown of TXN1 alone elevated radiosensitivity across multiple cell lines, establishing TXN1 as an essential pro-survival effector in the radiation response. Luciferase reporter assay (direct target validation), RNAi knockdown, miR-525-3p overexpression/inhibition, proteomic identification of targets, multi-cell-line validation PloS one Medium 24147004
2018 TRX-1 overexpression in an MPTP mouse model of Parkinson's disease ameliorates learning and memory deficits via the dopamine D1 receptor/NMDAR-ERK1/2-CREB pathway: Trx-1 transgenic mice showed restored TH and D1R expression, increased NR2B, and elevated p-ERK1/2 and p-CREB in the hippocampus compared to wild-type MPTP-treated mice. Trx-1 transgenic mouse model, Morris water maze, elevated plus-maze, Western blot for TH, D1R, NR2B, p-ERK1/2, p-CREB Free radical biology & medicine Medium 29960099
2023 TxN (thioredoxin) synthesis is linked to BCAA catabolism in glioblastoma: glutamate produced by BCAA catabolism (via BCAT1) participates in antioxidant TxN production; nuclear translocation of LDHA promotes DOT1L-mediated H3K79 hypermethylation and enhanced BCAT1/BCAA catabolism under ROS accumulation, establishing a metabolic pathway linking BCAA catabolism to TxN-mediated redox balance in GBM. Orthotopic xenograft model, BCAT1 inhibition, nuclear LDHA fractionation, H3K79 methylation ChIP, ROS measurement, glutamate/TxN quantification International journal of molecular sciences Low 37298317

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis. The EMBO journal 258 11927553
2018 Dl-3-n-Butylphthalide Inhibits NLRP3 Inflammasome and Mitigates Alzheimer's-Like Pathology via Nrf2-TXNIP-TrX Axis. Antioxidants & redox signaling 166 29634349
1996 A novel promoter sequence is involved in the oxidative stress-induced expression of the adult T-cell leukemia-derived factor (ADF)/human thioredoxin (Trx) gene. Nucleic acids research 109 8759006
2010 Activation of apoptosis signal-regulating kinase 1 is a key factor in paraquat-induced cell death: modulation by the Nrf2/Trx axis. Free radical biology & medicine 107 20202476
2020 Enhanced Keap1-Nrf2/Trx-1 axis by daphnetin protects against oxidative stress-driven hepatotoxicity via inhibiting ASK1/JNK and Txnip/NLRP3 inflammasome activation. Phytomedicine : international journal of phytotherapy and phytopharmacology 97 32454347
2003 Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues. Cell biology and toxicology 95 14703116
2002 MLL3, a new human member of the TRX/MLL gene family, maps to 7q36, a chromosome region frequently deleted in myeloid leukaemia. Gene 93 11891048
1995 Induction of ADF/TRX by oxidative stress in keratinocytes and lymphoid cells. Immunology letters 90 7797250
2018 β-Sitosterol targets Trx/Trx1 reductase to induce apoptosis in A549 cells via ROS mediated mitochondrial dysregulation and p53 activation. Scientific reports 86 29391428
2006 Renal cell carcinoma with nodal metastases in the absence of distant metastatic disease (clinical stage TxN1-2M0): the impact of aggressive surgical resection on patient outcome. The Journal of urology 86 16469567
1999 MLL2: A new mammalian member of the trx/MLL family of genes. Genomics 84 10409430
1994 Neuroprotection by glial cells through adult T cell leukemia-derived factor/human thioredoxin (ADF/TRX). Brain research 81 7953744
2019 FOXO1 Overexpression Attenuates Tubulointerstitial Fibrosis and Apoptosis in Diabetic Kidneys by Ameliorating Oxidative Injury via TXNIP-TRX. Oxidative medicine and cellular longevity 76 30962862
2018 Perilla aldehyde attenuates CUMS-induced depressive-like behaviors via regulating TXNIP/TRX/NLRP3 pathway in rats. Life sciences 76 29800538
2019 Resveratrol Suppresses Aβ-Induced Microglial Activation Through the TXNIP/TRX/NLRP3 Signaling Pathway. DNA and cell biology 75 31215797
2009 Intrinsic flexibility of B-DNA: the experimental TRX scale. Nucleic acids research 72 19920127
2001 Serum thioredoxin (TRX) levels in patients with heart failure. Japanese circulation journal 71 11407728
2008 Changes of MMP-1 and collagen type Ialpha1 by UVA, UVB and IRA are differentially regulated by Trx-1. Experimental gerontology 70 18524517
2002 Thioredoxin-2 but not thioredoxin-1 is a substrate of thioredoxin peroxidase-1 from Drosophila melanogaster: isolation and characterization of a second thioredoxin in D. Melanogaster and evidence for distinct biological functions of Trx-1 and Trx-2. The Journal of biological chemistry 70 11877442
2006 Inhibition of transforming growth factor-beta1-induced signaling and epithelial-to-mesenchymal transition by the Smad-binding peptide aptamer Trx-SARA. Molecular biology of the cell 69 16775010
2005 Lifespan decrease in a Caenorhabditis elegans mutant lacking TRX-1, a thioredoxin expressed in ASJ sensory neurons. FEBS letters 69 16387300
2014 Nicotinamide nucleotide transhydrogenase (Nnt) links the substrate requirement in brain mitochondria for hydrogen peroxide removal to the thioredoxin/peroxiredoxin (Trx/Prx) system. The Journal of biological chemistry 67 24722990
2001 Truncated thioredoxin (Trx80) induces production of interleukin-12 and enhances CD14 expression in human monocytes. Blood 61 11342447
2016 An Evolutionary Conserved Epigenetic Mark of Polycomb Response Elements Implemented by Trx/MLL/COMPASS. Molecular cell 59 27447986
2024 Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases. Redox biology 57 38232457
2020 Targeting the MAPK/ERK and PI3K/AKT Signaling Pathways Affects NRF2, Trx and GSH Antioxidant Systems in Leukemia Cells. Antioxidants (Basel, Switzerland) 57 32709140
2017 Brain-Derived Neurotrophic Factor Increases Synaptic Protein Levels via the MAPK/Erk Signaling Pathway and Nrf2/Trx Axis Following the Transplantation of Neural Stem Cells in a Rat Model of Traumatic Brain Injury. Neurochemical research 57 28780733
2008 Hexameric oligomerization of mitochondrial peroxiredoxin PrxIIF and formation of an ultrahigh affinity complex with its electron donor thioredoxin Trx-o. Journal of experimental botany 52 18632730
2018 Trx-1 ameliorates learning and memory deficits in MPTP-induced Parkinson's disease model in mice. Free radical biology & medicine 46 29960099
2000 Upregulation of thioredoxin (TRX) expression in giant cell myocarditis in rats. FEBS letters 46 10781815
1989 Chromosomal location of the Bacillus subtilis aspartokinase II gene and nucleotide sequence of the adjacent genes homologous to uvrC and trx of Escherichia coli. Journal of general microbiology 46 2559145
2019 Salvianolic acid A attenuated myocardial infarction-induced apoptosis and inflammation by activating Trx. Naunyn-Schmiedeberg's archives of pharmacology 41 31811327
2015 The overexpression and nuclear translocation of Trx-1 during hypoxia confers on HepG2 cells resistance to DDP, and GL-V9 reverses the resistance by suppressing the Trx-1/Ref-1 axis. Free radical biology & medicine 40 25656992
2013 SCO2 induces p53-mediated apoptosis by Thr845 phosphorylation of ASK-1 and dissociation of the ASK-1-Trx complex. Molecular and cellular biology 39 23319048
2016 Low-Intensity Pulsed Ultrasound Enhances Nerve Growth Factor-Induced Neurite Outgrowth through Mechanotransduction-Mediated ERK1/2-CREB-Trx-1 Signaling. Ultrasound in medicine & biology 38 27592560
2015 Methylglyoxal, the foe and friend of glyoxalase and Trx/TrxR systems in HT22 nerve cells. Free radical biology & medicine 38 26165190
2016 FOXO1 is a TXN- and p300-dependent sensor and effector of oxidative stress in diffuse large B-cell lymphomas characterized by increased oxidative metabolism. Oncogene 36 27132507
2015 GL-V9, a new synthetic flavonoid derivative, ameliorates DSS-induced colitis against oxidative stress by up-regulating Trx-1 expression via activation of AMPK/FOXO3a pathway. Oncotarget 36 26327408
2004 Cysteine-dependent immune regulation by TRX and MIF/GIF family proteins. Immunology letters 36 15081538
2013 Nitrosative/oxidative stress conditions regulate thioredoxin-interacting protein (TXNIP) expression and thioredoxin-1 (TRX-1) nuclear localization. PloS one 35 24376827
2011 The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans. Biochemical and biophysical research communications 35 21334311
2021 Ligustrazine alleviates cyclophosphamide-induced hepatotoxicity via the inhibition of Txnip/Trx/NF-κB pathway. Life sciences 34 33716060
2017 Silymarin attenuated paraquat-induced cytotoxicity in macrophage by regulating Trx/TXNIP complex, inhibiting NLRP3 inflammasome activation and apoptosis. Toxicology in vitro : an international journal published in association with BIBRA 34 29054699
2009 Direct association of thioredoxin-1 (TRX) with macrophage migration inhibitory factor (MIF): regulatory role of TRX on MIF internalization and signaling. Antioxidants & redox signaling 34 19601712
2023 Astragalus polysaccharides ameliorate osteoarthritis via inhibiting apoptosis by regulating ROS-mediated ASK1/p38 MAPK signaling pathway targeting on TXN. International journal of biological macromolecules 33 38151083
2017 Troxerutin (TXN) potentiated 5-Fluorouracil (5-Fu) treatment of human gastric cancer through suppressing STAT3/NF-κB and Bcl-2 signaling pathways. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 33 28531805
2010 Loss of Trx-2 enhances oxidative stress-dependent phenotypes in Drosophila. FEBS letters 33 20600005
2006 Redox regulation of mast cell histamine release in thioredoxin-1 (TRX) transgenic mice. Cell research 33 16474438
2017 Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes. International journal of nanomedicine 32 28848346
2003 Truncated thioredoxin (Trx80) exerts unique mitogenic cytokine effects via a mechanism independent of thiol oxido-reductase activity. FEBS letters 32 12650942
2004 Truncated thioredoxin (Trx80) induces differentiation of human CD14+ monocytes into a novel cell type (TAMs) via activation of the MAP kinases p38, ERK, and JNK. Blood 31 15494431
2000 Pc-G/trx-G and the SWI/SNF connection: developmental gene regulation through chromatin remodeling. Genesis (New York, N.Y. : 2000) 31 10705379
2021 Anti-oxidant, anti-inflammatory and anti-fibrosis effects of ganoderic acid A on carbon tetrachloride induced nephrotoxicity by regulating the Trx/TrxR and JAK/ROCK pathway. Chemico-biological interactions 30 34029542
2022 TXN inhibitor impedes radioresistance of colorectal cancer cells with decreased ALDH1L2 expression via TXN/NF-κB signaling pathway. British journal of cancer 29 35597868
2021 PKC Delta Activation Promotes Endoplasmic Reticulum Stress (ERS) and NLR Family Pyrin Domain-Containing 3 (NLRP3) Inflammasome Activation Subsequent to Asynuclein-Induced Microglial Activation: Involvement of Thioredoxin-Interacting Protein (TXNIP)/Thioredoxin (Trx) Redoxisome Pathway. Frontiers in aging neuroscience 29 34276337
2018 Interplay between Trx-1 and S100P promotes colorectal cancer cell epithelial-mesenchymal transition by up-regulating S100A4 through AKT activation. Journal of cellular and molecular medicine 29 29383839
2014 Hyperglycemia regulates TXNIP/TRX/ROS axis via p38 MAPK and ERK pathways in pancreatic cancer. Current cancer drug targets 28 24720336
2020 One cysteine is enough: A monothiol Grx can functionally replace all cytosolic Trx and dithiol Grx. Redox biology 27 32521506
2016 TXNIP/TRX/NF-κB and MAPK/NF-κB pathways involved in the cardiotoxicity induced by Venenum Bufonis in rats. Scientific reports 27 26961717
2013 LW-214, a newly synthesized flavonoid, induces intrinsic apoptosis pathway by down-regulating Trx-1 in MCF-7 human breast cells. Biochemical pharmacology 27 24374359
2019 The thioredoxin (Trx) redox state sensor protein can visualize Trx activities in the light/dark response in chloroplasts. The Journal of biological chemistry 26 31217277
2013 Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis. Journal of cellular physiology 26 23335265
2016 Expression of thioredoxin-1 (TXN) and its relation with oxidative DNA damage and treatment outcome in adult AML and ALL: A comparative study. Hematology (Amsterdam, Netherlands) 25 27158980
2020 Estrogen protects neuroblastoma cell from amyloid-β 42 (Aβ42)-induced apoptosis via TXNIP/TRX axis and AMPK signaling. Neurochemistry international 24 31931042
2019 Diagnostic value analysis of combined detection of Trx, CYFRA21-1 and SCCA in lung cancer. Oncology letters 24 30944623
2008 TRX-ASK1-JNK signaling regulation of cell density-dependent cytotoxicity in cigarette smoke-exposed human bronchial epithelial cells. American journal of physiology. Lung cellular and molecular physiology 24 18281606
1995 The human MLL gene: nucleotide sequence, homology to the Drosophila trx zinc-finger domain, and alternative splicing. DNA and cell biology 24 7598802
2016 TRX-E-002-1 Induces c-Jun-Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo. Molecular cancer therapeutics 23 27196760
2006 dDYRK2 and Minibrain interact with the chromatin remodelling factors SNR1 and TRX. The Biochemical journal 23 16671894
2017 Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress. Neurotoxicology 22 28082123
2016 Taurine protects against As2O3-induced autophagy in pancreas of rat offsprings through Nrf2/Trx pathway. Biochimie 22 26775255
2004 PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12. Blood 22 15507528
2020 Different Intensity Exercise Preconditions Affect Cardiac Function of Exhausted Rats through Regulating TXNIP/TRX/NF-ĸBp65/NLRP3 Inflammatory Pathways. Evidence-based complementary and alternative medicine : eCAM 21 32595731
2001 corto genetically interacts with Pc-G and trx-G genes and maintains the anterior boundary of Ultrabithorax expression in Drosophila larvae. Molecular genetics and genomics : MGG 21 11810228
2019 Regulation of cartilage damage caused by lack of Klotho with thioredoxin/peroxiredoxin (Trx/Prx) system and succedent NLRP3 activation in osteoarthritis mice. American journal of translational research 20 31934282
2016 Ruxolitinib synergizes with DMF to kill via BIM+BAD-induced mitochondrial dysfunction and via reduced SOD2/TRX expression and ROS. Oncotarget 20 26981780
2016 Ischemic postconditioning confers cardioprotection and prevents reduction of Trx-1 in young mice, but not in middle-aged and old mice. Molecular and cellular biochemistry 19 26932791
2013 Functional characterization of thioredoxin 3 (TRX-3), a Caenorhabditis elegans intestine-specific thioredoxin. Free radical biology & medicine 19 24316195
2002 A new family of cyclophilins with an RNA recognition motif that interact with members of the trx/MLL protein family in Drosophila and human cells. Development genes and evolution 19 11976948
2016 Coordinate Activation of Redox-Dependent ASK1/TGF-β Signaling by a Multiprotein Complex (MPK38, ASK1, SMADs, ZPR9, and TRX) Improves Glucose and Lipid Metabolism in Mice. Antioxidants & redox signaling 18 26421442
2015 Sodium tanshinone IIA sulfonate suppresses pulmonary fibroblast proliferation and activation induced by silica: role of the Nrf2/Trx pathway. Toxicology research 18 30090331
2011 The thioredoxin TRX-1 modulates the function of the insulin-like neuropeptide DAF-28 during dauer formation in Caenorhabditis elegans. PloS one 18 21304598
1997 The effect of ultraviolet B induced adult T cell leukemia-derived factor/thioredoxin (ADF/TRX) on survival and growth of human melanocytes. Pigment cell research 18 9170166
2020 Relationships between diabetic nephropathy and insulin resistance, inflammation, Trx, Txnip, CysC and serum complement levels. European review for medical and pharmacological sciences 17 33275238
2016 TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans. Genetics 17 26920757
2002 Redox regulation of stress signals: possible roles of dendritic stellate TRX producer cells (DST cell types). Biological chemistry 17 12033447
2016 Protective function of pyridoxamine on retinal photoreceptor cells via activation of the p‑Erk1/2/Nrf2/Trx/ASK1 signalling pathway in diabetic mice. Molecular medicine reports 16 27177199
2013 Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury. PloS one 16 24223778
2007 Investigation of TXNIP (thioredoxin-interacting protein) and TRX (thioredoxin) genes for growth-related traits in pigs. Mammalian genome : official journal of the International Mammalian Genome Society 16 17406940
2023 Nuclear Translocation of LDHA Promotes the Catabolism of BCAAs to Sustain GBM Cell Proliferation through the TxN Antioxidant Pathway. International journal of molecular sciences 15 37298317
2023 TrxR/Trx inhibitor butaselen ameliorates pulmonary fibrosis by suppressing NF-κB/TGF-β1/Smads signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 37944440
2023 Irisin suppresses pancreatic β cell pyroptosis in T2DM by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis. Diabetology & metabolic syndrome 15 37993958
2020 Neuroprotective effects of notoginsenoside R1 by upregulating Trx-1 on acrylamide-induced neurotoxicity in PC12. Human & experimental toxicology 15 31971015
2016 Predictive value of ATP7b, BRCA1, BRCA2, PARP1, UIMC1 (RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) genes in patients with epithelial ovarian cancer who received platinum-taxane first-line therapy. The pharmacogenomics journal 15 27779244
2016 Txn1, Ctsd and Cdk4 are key proteins of combination therapy with taurine, epigallocatechin gallate and genistein against liver fibrosis in rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 27894668
2007 Expression and extracellular release of Trx80, the truncated form of thioredoxin, by TNF-alpha- and IL-1beta-stimulated human synoviocytes from patients with rheumatoid arthritis. Clinical science (London, England : 1979) 15 17447898
2020 Molecular and functional explication of thioredoxin mitochondrial-like protein (Trx-2) from big-belly seahorse (Hippocampus abdominalis) and expression upon immune provocation. Fish & shellfish immunology 14 32081809
2011 Functional characterization of the recombinant antimicrobial peptide Trx-Ace-AMP1 and its application on the control of tomato early blight disease. Applied microbiology and biotechnology 14 21380518
2005 Synergistic action of MLL, a TRX protein with template activating factor-I, a histone chaperone. FEBS letters 14 15670842
2013 Cell survival following radiation exposure requires miR-525-3p mediated suppression of ARRB1 and TXN1. PloS one 13 24147004

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